Capsular serotype in group B Streptococcus colonization and disease

B 组链球菌定植和疾病中的荚膜血清型

• 批准号: 10620312
• 负责人: Adam Jonathan Ratner
• 金额: $ 70.25万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-08 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10620312
• 关键词: Active Sites; Address; Adult; Alleles; Animal Model; Antibiotics; Bacterial Genes; Biological Assay; Biology; Characteristics; Clinical; Conjugate Vaccines; Data; Disease; Epidemiology; Etiology; Frequencies; Genes; Genetic; Genome; Genomics; Goals; Human; Infant; Infection; Laboratories; Metadata; Morbidity - disease rate; Mutation; Neonatal; Newborn Infant; Pathogenesis; Pathogenicity; Polysaccharides; Population; Pregnant Women; Prevalence; Prevention; Prophylactic treatment; Prospective Studies; Research; Research Design; Risk; Risk Factors; Role; Sampling; Serotyping; Streptococcal Infections; Streptococcus Group B; System; Techniques; Testing; Vaccination; Vaccines; antimicrobial; bacterial genetics; candidate identification; capsule; comparative; cost; epidemiology study; fitness; genome sequencing; genomic locus; in vivo; intrapartum; mortality; mouse model; mutant; neonatal sepsis; programs; screening; screening program; success; tool; vaccine candidate; vaccine development; whole genome

Despite ongoing surveillance and control efforts, group B Streptococcus (GBS) remains an important cause of infectious morbidity and mortality among newborns, as well as an increasing cause of invasive disease in adults. GBS vaccine development is a high priority, and a candidate conjugate polysaccharide vaccine is currently in human trials. This vaccine targets six of the ten known GBS serotypes, based on epidemiologic studies of invasive disease as well as rectovaginal carriage. Serotype distribution data are largely based on assays of single colonies from clinical samples. Based on our preliminary data, we hypothesize that carriage of non- vaccine type (NVT) GBS (serotypes VI-IX) is substantially more common than previously realized. Additionally, invasive infections due to NVT GBS are increasing in frequency. It is not known whether the less common GBS serotypes are intrinsically less fit than the more common ones with respect to colonization efficiency or pathogenicity. Likewise, the importance of recently characterized naturally occurring "capsule switch" GBS strains, in which the genetic locus that determines capsular type has transferred from one strain to another, remains incompletely understood. Here we propose a program of research designed to test hypotheses regarding the prevalence of (and risk factors for) colonization and invasive infection due to NVT GBS serotypes in human samples and to use newly developed techniques for GBS genome manipulation to understand the role of specific capsule and non-capsule factors in colonization fitness and pathogenesis in vivo.

尽管正在进行监测和控制努力，B组链球菌(GBS)仍然是一种 新生儿感染发病率和死亡率的重要原因，以及不断增加的 成人侵袭性疾病的原因。GBS疫苗的开发是一个高度优先的问题，而且 候选结合多糖疫苗目前正在进行人体试验。这种疫苗的目标是六个 在已知的10种GBS血清型中，基于侵袭性疾病的流行病学研究以及 直肠到阴道的马车。血清型分布数据在很大程度上是基于单个菌落的分析 从临床样本中提取。根据我们的初步数据，我们假设运输的非 疫苗类型(NVT)GBS(血清型VI-IX型)比以前更常见 意识到了。此外，由NVT GBS引起的侵袭性感染的频率正在增加。它不是 是否知道不太常见的GBS血清型本身就不太适合较常见的GBS 与定殖率或致病性有关的。同样，重要的是 最近表征了自然发生的“胶囊开关”GBS菌株，其中基因 决定包膜类型从一种菌株转移到另一种菌株的基因座仍然存在 不完全理解。在这里，我们提出了一个旨在检验假设的研究计划 关于NVT引起的殖民和侵袭性感染的流行率(和风险因素) 人类样本中的GBS血清分型和使用新开发的GBS基因组技术 了解特定包膜和非包膜因子在定植中的作用的操作 适合性和体内致病机制。

项目成果

A group B Streptococcus indexed transposon mutant library to accelerate genetic research on an important perinatal pathogen.

• DOI: 10.1128/spectrum.02046-23
• 发表时间: 2023-12-12
• 期刊: MICROBIOLOGY SPECTRUM
• 影响因子: 3.7
• 作者: Bhavana, Venkata H.;Hillebrand, Gideon H.;Gopalakrishna, Kathyayini P.;Rapp, Rebekah A.;Ratner, Adam J.;Tettelin, Herve;Hooven, Thomas A.
• 通讯作者: Hooven, Thomas A.